The proposed research is designed to gain a better understanding of the regulation of central nervous system (CNS) acid-base and electrolyte homeostasis. The CNS acid-base status, in turn, has an important effect on the central chemical ventilatory drive. Regulation of the cerebrospinal fluid (CSF) chloride concentration likely plays an important role in CNS acid-base homeostasis, yet the mechanisms underlying its control remain uncertain. The role of net flux of chloride will be evaluated by studying the CSF electrolyte and acid-base composition following administration of chloride transport inhibitors and/or acid-base disturbances in anesthetized dogs. Quantitative estimates of the individual unidirectional fluxes of radiolabelled chloride between blood, CSF, brain ECF in anesthetized dogs will be made. The use of a short half-lived isotope, will allow multiple studies to be performed in a given animal, permitting each animal to serve as its own control. By studying the effects of chloride transport inhibitors and acid-base status, a good understanding of the role of chloride movements in CNS acid-base regulation will be gained which will have direct relevance to central drive to respiration in normal and disease states.